1. Field of the Invention
This invention relates to liquid compositions of anesthetic agents in aerosol containers. More specifically, this invention relates to liquid compositions of the anesthetic benzocaine which form single phase mixtures in combination with solvent and hydrocarbon propellants, and which remain single phase at low temperatures and high concentrations of benzocaine.
2. Description of Related Art
Benzocaine, the ethyl ester, ester of p-aminobenzoic acid, is a well known local anesthetic which has been topically administered in the form of ointments, lotions, sprays, gels and as an impregnant in first aid pads. In order to enhance or prolong benzocaine's anesthetic activity, various efforts have been made to increase the concentration of benzocaine in various solvents or to more effectively maintain the anesthetic at its site of administration. Increasing the concentration of benzocaine, however, had to be balanced against the increasing probability of benzocaine precipitation, particularly at colder temperatures, thereby limiting their field of use. The goal of formulating highly concentrated benzocaine compositions characterized by cold temperature resistance is even greater in aerosol anesthetic compositions wherein even small amounts of precipitate can clog valves or orifices, and wherein sufficient pressure must be maintained to both completely deliver all the benzocaine solution within the container and evenly distribute the benzocaine solution with desirable spray characteristics.
Many solvents have been disclosed for benzocaine. For example, U.S. Pat. No. 2,187,597 discloses anesthetic formulations containing up to five percent of the anesthetic agent in a mixture of benzyl alcohol and ethyl chloride. Other formulations containing up to 10% benzocaine in mixtures with a procaine salt, water, water miscible poly-hydroxy aliphathic alcohols and their ethers have been disclosed in U.S. Pat. No. 2,382,546. U.S. Pat. No. 2,457,188 discloses benzocaine solutions containing at least 10% benzocaine at 20.degree. C. utilizing solvents selected from certain polyoxyalkylene glycols, aliphatic ethers of dihydric alcohols, aromatic ethers of aliphatic dihydric alcohols, carboxylic acid esters of aliphatic dihydric alcohols, and carboxylic acid esters of aromatic and aliphatic ethers of aliphatic dihydric alcohols. In U.S. Pat. No. 2,682,182, benzocaine solutions containing up to 16% benzocaine at 0.degree. C. were disclosed in a mixture employing a major amount of propylene glycol and a polyoxyethylene (8-25) hexitan monolaurate.
Anesthetic aerosol preparations containing at least 10% benzocaine in diesters of C.sub.8 -C.sub.12 carboxylic acids and polyethylene glycols having a molecular weight of appoximately 300-600, and a propellant system made from mixture of chlorofluorohydrocarbons have been disclosed in U.S. Pat. No. 3,322,634. These aerosol formulations, however, are no longer acceptable because of certain atmospheric effects associated with chlorofluorohydrocarbons.
Benzocaine has also been employed in formulations containing certain other therapeutic ingredients, for example, as disclosed in U.S. Pat. No. 3,808,319 wherein the solvent is volatile alcohol such as ethyl alcohol or isopropyl alcohol. Solvents of this type, however, are generally counterproductive to desirable anesthetic properties because of their stinging nature to sensitive or wounded skin and the like. Compositions containing up to 15% benzocaine are further disclosed in U.S. Pat. No. 4,052,513 in the form of oil in water emulsions.